Immunoregulation Section, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH, 10 Center Drive, Bethesda, MD 20892-1930, USA.
Nat Rev Rheumatol. 2011 Mar;7(3):152-60. doi: 10.1038/nrrheum.2010.225. Epub 2011 Feb 1.
Programmed cell death (PCD) is a key process in the regulation of immune cell development and peripheral immune homeostasis. Caspase-dependent apoptosis, as well as a number of alternative cell death mechanisms, account for immune cell PCD induced by cell-intrinsic and extrinsic pathways. In animal models, compelling evidence has emerged that genetic defects in PCD can result in autoimmune disease. Autoimmune disease can arise from single-gene mutations that affect PCD, and defective PCD has been observed in some tissues and cells from patients with rheumatic disease. Selectively inducing PCD in autoreactive B and T cells is very attractive as a therapeutic strategy because it offers the possibility of permanent elimination of these pathogenic cell subsets. In addition, the anti-inflammatory effects of apoptotic cells may add to the therapeutic benefit of induced PCD. Immune cell subsets vary widely in their sensitivity to specific inducers of cell death, and understanding these differences is key to predicting the outcome of inducing apoptosis for therapeutic means. Here, we review approaches that have been used to induce PCD in the treatment of autoimmune disease, and describe the prospects of bringing these experimental strategies into clinical practice.
程序性细胞死亡 (PCD) 是调节免疫细胞发育和外周免疫稳态的关键过程。依赖半胱天冬酶的细胞凋亡以及许多替代细胞死亡机制，解释了细胞内和细胞外途径诱导的免疫细胞 PCD。在动物模型中，有强有力的证据表明 PCD 的遗传缺陷可导致自身免疫性疾病。自身免疫性疾病可能源于影响 PCD 的单基因突变，并且在风湿性疾病患者的某些组织和细胞中观察到 PCD 缺陷。选择性诱导自身反应性 B 和 T 细胞的 PCD 作为一种治疗策略非常有吸引力，因为它有可能永久性消除这些致病性细胞亚群。此外，凋亡细胞的抗炎作用可能会增加诱导 PCD 的治疗益处。免疫细胞亚群对特定细胞死亡诱导剂的敏感性差异很大，了解这些差异是预测诱导细胞凋亡用于治疗目的的结果的关键。在这里，我们回顾了用于治疗自身免疫性疾病的诱导 PCD 的方法，并描述了将这些实验策略引入临床实践的前景。
